Smad2 and Smad3 are signalling proteins that are involved in mediating the transcriptional regulation of target genes downstream of transforming growth factor-β and activin receptors. Although they are structurally very similar, Smad2 and Smad3 have some functional differences in transducing signals for these receptors. In FAST-2 (forkhead activin signal transducer-2)-mediated transcriptional regulation using the activin-responsive element derived from Xenopus Mix.2 promoter as a reporter, Smad3 but not Smad2 alone was able to stimulate the transcription. In addition, Smad3 was able to inhibit the transactivation of the promoter induced by co-expression of Smad2, Smad4 and an active activin type-I receptor. We used a series of chimaeras between Smad1 and Smad3 and found that the Mad homology 1 (MH1) domain of Smad3 was indispensable for the dual regulatory function of Smad3. However, this Smad3-specific function could not be manifested in Smad2 mutants that were devoid of the two amino acid insertions (at the MH1 domain) that comprise the major structural difference between Smad2 and Smad3, indicating that other structural motifs are involved in determining the regulatory activity of Smad3. By using chimaeras between Smad2 and Smad3, we found that the most N-terminal portion of Smad3 was crucial for its function. Taken together, these results suggest that, as compared with Smad2, the unique function of Smad3 in modulating the FAST-2-mediated transcription is contributed to by a subtle difference in the structural features at the MH1 domain.
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Research Article|
August 09 2000
Structural basis for the functional difference between Smad2 and Smad3 in FAST-2 (forkhead activin signal transducer-2)-mediated transcription
Raman P. NAGARAJAN;
Raman P. NAGARAJAN
1Department of Medical and Molecular Genetics and the Walther Oncology Center, Indiana University School of Medicine, 975 West Walnut Street, IB130, Indianapolis, IN 46202, U.S.A.
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Yan CHEN
Yan CHEN
1
1Department of Medical and Molecular Genetics and the Walther Oncology Center, Indiana University School of Medicine, 975 West Walnut Street, IB130, Indianapolis, IN 46202, U.S.A.
1To whom correspondence should be addressed (e-mail ychen3@iupui.edu).
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Publisher: Portland Press Ltd
Received:
February 09 2000
Revision Received:
May 10 2000
Accepted:
June 05 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 350 (1): 253–259.
Article history
Received:
February 09 2000
Revision Received:
May 10 2000
Accepted:
June 05 2000
Citation
Raman P. NAGARAJAN, Yan CHEN; Structural basis for the functional difference between Smad2 and Smad3 in FAST-2 (forkhead activin signal transducer-2)-mediated transcription. Biochem J 15 August 2000; 350 (1): 253–259. doi: https://doi.org/10.1042/bj3500253
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